Thiopurine methyltransferase genotype and thiopurine S-methyltransferase activity in Greek children with inflammatory bowel disease
Anagnou, Nicholas P.
Background Azathioprine (AZA) and 6-mercaptopurine (6MP) are used in the treatmentof pediatric inflammatory bowel disease (IBD). Genetic variations in thiopurineS-methyltranfarase (TPMT) gene have been correlated with enzyme activity and with theoccurrence of adverse events to AZA and 6MP. The aim of the present study was to examinethe sensitivity and specificity of TPMT genotyping for TPMT enzymatic activity, reducingharm from thiopurine by pretesting, and the association of thiopurine toxicity with TPMTstatus in children with IBD.Methods TPMT red blood cell (RBC) activity was measured by using a radiochemical methodand genotype was determined for the TPMT alleles *2, *3A, *3B and *3C in 108 thiopurinetreated pediatric IBD patients with a mean age of 11.3 years (range 3-16).Results Significant TPMT activity differences between wild-type and heterozygous and homozygous mutated subjects were observed. We divided TPMT activity into three categoriesaccording to frequency distribution: low (16.67%), intermediate (25.92%) and high (57.41%).The whole population included a total of 77.78% of homozygous wild-type subjects, 15.74%heterozygous variants, 1.85% homozygous variants and five (4.63%) compound heterozygousvariant TPMT*3B/*3C. The overall concordance rate between TPMT genotypes and phenotypeswas 88.2%. Seven carriers of at least one variant allele and low or intermediate TPMT activitydeveloped adverse effects.Conclusions Our findings suggest that carriers of at least one variant allele and both intermediate and absent TPMT activity have an increased risk of developing thiopurine-inducedmyelotoxicity compared with individuals with normal genotype and TPMT activity.Keywords azathioprine, 6MP, pharmacogenetics, TPMT, inflammatory bowel diseaseAnn Gastroenterol 2012; 25 (3): 249-253